Cervical Cancer - Putting Anti-Viral White Blood Cells To Work

December 01, 1997

The association between some strains of the human papillomavirus (HPV) and cervical cancer is greater than that between smoking and lung cancer. At the British Society for Immunology Annual Congress in Brighton this week, Dr Stephen Man from the University of Wales College of Medicine, Cardiff will explain how he hopes the body's own defence system can be mobilised against HPV to prevent and treat cervical cancer.

The first task for Dr Man and his co-workers has been to understand natural immunity to HPV and its role in controlling disease. They studied a group of women with an early, preinvasive form of the cancer called cervical epithelial neoplasia (CIN3). In approximately 30% of women with this condition the precancerous cells are cleared from the body without any treatment. Could this be a sign of the immune system at work?

To try to answer this question the Cardiff researchers had to find a way to detect white blood cells (lymphocytes) which could recognise and respond to HPV. Having developed a novel technique to do so they have shown that between 30-50% of women with CIN3 have killer lymphocytes recognising HPV in their blood. Volunteers without the disease had none.

However, it's not enough to have killer lymphocytes. They also have to be able to home in on the cancerous tissue. In their studies, Dr Man and his colleagues have shown that the killer lymphocytes are found in the tumour and surrounding tissues. Preliminary results suggest that there is a higher concentration of these lymphocytes in the tumour than in the blood. But if the lymphocytes are present, why do tumours develop? The researchers plan to answer this by studying the interactions between tumour cells and lymphocytes both inside and outside the body.

One way in which this knowledge could be used in the treatment of cervical cancer is to grow large numbers of the killer lymphocytes in the lab. These could then be transfused into patients with the disease to give their own immune cells a helping hand. The Cardiff team is currently identifying proteins which are specific to these lymphocytes. This will allow them to "tag" the transfused cells and follow their progress around the body.

A second approach has been to boost the number of killer lymphocytes by vaccination. Cantab Pharmaceuticals, Cambridge, UK, have developed a recombinant viral vaccine which includes portions of the two strains of HPV associated most closely with cervical cancer. Preliminary results from a recent clinical trial run by the Welsh researchers suggest that the vaccine was able to generate killer lymphocytes in the bodies of several women with CIN3. Trials of the vaccine are now underway in patients with early stage invasive cervical cancer at several centres across Europe, including Cardiff.

Notes:
1. Dr Man is speaking in the Immunity and Cancer session on Tuesday 2 December. The BSI 5th Annual Congress is at the Brighton Centre from 2-5 December 1997.
2. Dr Man can be contacted at the Department of Medicine, Tenovus Building, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XX Wales, UK Tel: +44 1222 745 256 or 745 004 Fax: +44 1222 745 003 ManS@cardiff.ac.uk
3. Cantab Pharmaceuticals can be contacted via Melissa Hellberg Vice-president of Investor and Media Relations, Cantab Pharmaceuticals, 184 Cambridge Science Park, Cambridge CB4 4GN UK.Tel: +44 1223 423413 ext 454 Fax: +44 1223 423 458 In addition Dr Julian Hickling from the company will be attending the meeting.
4. There will be a press office at the meeting in operation from 9am on Tuesday 2 December, tel: +44 1273 724 320. Journalists are welcome to attend but are requested to contact Kirstie Urquhart in advance to register.


Appendix

Human papillomaviruses (HPVs) are a large family of viruses that infect cells of the skin. Certain HPVs such as HPV16 and HPV18 are known as "high risk" viruses because they are strongly associated with the development of cervical cancer. A recent survey by the World Health Organisation has found that genetic material (DNA) from "high risk" HPVs can be found in greater than 94% of cervical cancers, an association that is greater than that between smoking and lung cancer. Screening programs for precancerous cells in the cervix (cervical smear test) have been very effective in reducing the incidence of cervical cancer in many countries. Nevertheless cervical cancer still has a major public health impact being responsible for 500,000 deaths worldwide per annum, with approximately 1400 deaths per annum in the UK. The strong association between HPV and cervical cancer has lead to much study on the immune response to HPV with the aim of developing vaccines. Such vaccines could take two forms. The first would be a preventative vaccine to alert the immune system to prevent infection of cervical cells by HPV. This could be particularly effective in developing countries which do not have screening programs and where 80% of cervical cancers occur. The second type would be a therapeutic vaccine, to treat women who already have cancer. Such a vaccine would activate killer lymphocytes which would recognise and destroy cervical cells which have become cancerous after infection by HPV. Research in Cardiff is centred on developing rational therapies for cervical cancer using killer lymphocytes which recognise HPV infected cancer cells.

British Society For Immunology

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